title: Lipidomic profiling of bioactive lipids by mass spectrometry during microbial infections.
abstract: Bioactive lipid mediators play crucial roles in promoting the induction and resolution of inflammation. Eicosanoids and other related unsaturated fatty acids have long been known to induce inflammation. These signaling molecules can modulate the circulatory system and stimulate immune cell infiltration into the site of infection. Recently, DHA- and EPA-derived metabolites have been discovered to promote the resolution of inflammation, an active process. Not only do these molecules stop the further infiltration of immune cells, they prompt non-phlogistic phagocytosis of apoptotic neutrophils, stimulating the tissue to return to homeostasis. After the rapid release of lipid precursors from the plasma membrane upon stimulation, families of enzymes in a complex network metabolize them to produce a large array of lipid metabolites. With current advances in mass spectrometry, the entire lipidome can be accurately quantified to assess the immune response upon microbial infection. In this review, we discuss the various lipid metabolism pathways in the context of the immune response to microbial pathogens, as well as their complex network interactions. With the advancement of mass spectrometry, these approaches have also been used to characterize the lipid mediator response of macrophages and neutrophils upon immune stimulation in vitro. Lastly, we describe the recent efforts to apply systems biology approaches to dissect the role of lipid mediators during bacterial and viral infections in vivo.
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA. Electronic address: vincent.tam@seattlebiomed.org.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Tam
mesh_terms: D000818:Animals; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007239:Infections / Q000276:immunology / Q000378:metabolism*; D050356:Lipid Metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D013058:Mass Spectrometry / Q000379:methods* / Q000639:trends; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D049490:Systems Biology / Q000379:methods* / Q000639:trends
chemical_list: D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: AA; AIM2-like receptor; ALR; Anti-inflammatory; Borrelia burgdorferi; CFU; COX; CYP450; DDXs/DHXs; DExD/H box proteins; DHA; E. coli; EET; EPA; ESI; EpOME; GM–MS; HDoHE; HEPE; HETE; HODE; HOTrE; HPLC; HXA(3)/B(3); Influenza; IκB; LC–MS; LOX; LT; LXA(4)/B(4); Lipid mediators; Lipidomic analysis; Lyme disease; MRM; Mass spectrometry; NFκB; NLR; NOD-like receptor; NSAIDs; PAF; PD1; PG; PMN; PPAR; PRRs; Peritonitis; Pro-resolution; Proinflammatory; RIG-I like receptor; RLR; Systems biology; TLR; TNF; TXA(2)/B(2); UDP; arachidonic acid; colony forming units; cyclooxygenase; cytochrome P450; diHETrE; diHOME; dihydroxy-eicosatrienoic acids; dihydroxy-octadecenoic acids; docosahexaenoic acids; eicosapentaenoic acid; electrospray ionization; epoxy-eicosatrienoic acids; epoxy-octadecenoic acids; gas chromatography coupled with mass spectrometry; hepoxilin A3/B3; high performace liquid chromatography; hydrox-eicosapentaenoic acids; hydroxy-docosahexaenoic acid; hydroxy-eicosatetraenoic acids; hydroxy-octadecadienoic acids; hydroxy-octadecatrienoic acids; inhibitor of kappa B; leukotriene; lipoxin A4/B4; lipoxygenase; liquid chromatography coupled with mass spectrometry; multiple reaction monitoring; non-steroidal anti-inflammatory drugs; nuclear factor kappa B; oxo-octadecadienoic acid; oxoODE; pattern recognition receptors; peroxisome proliferator-activated receptor; platelet-activating factor; polymorphonuclear cells; prostaglandin; protectin D1; thromboxane A2/B2; toll-like receptor; tumor necrosis factor; uridine 5′-diphosphate